Thematic review series: Adipocyte Biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease

Abstract

In the context of obesity and its related maladies, the adipocyte plays a central role in the balance, or imbalance, of metabolic homeostasis. An obese, hypertrophic adipocyte is challenged by many insults, including surplus energy, inflammation, insulin resistance, and considerable stress to various organelles. The endoplasmic reticulum (ER) is one such vital organelle that demonstrates significant signs of stress and dysfunction in obesity and insulin resistance. Under normal conditions, the ER must function in the unique and trying environment of the adipocyte, adapting to meet the demands of increased protein synthesis and secretion, energy storage in the form of triglyceride droplet formation, and nutrient sensing that are particular to the differentiated fat cell. When nutrients are in pathological excess, the ER is overwhelmed and the unfolded protein response (UPR) is activated. Remarkably, the consequences of UPR activation have been causally linked to the development of insulin resistance through a multitude of possible mechanisms, including c-jun N-terminal kinase activation, inflammation, and oxidative stress. This review will focus on the function of the ER under normal conditions in the adipocyte and the pathological effects of a stressed ER contributing to adipocyte dysfunction and a thwarted metabolic homeostasis.-Gregor, M. F., and G. S. Hotamisligil. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J. Lipid Res.

A unifying biologic explanation for “high‐sensitivity” C‐reactive protein and “low‐grade” inflammation

“…A thorough review of the molecular mechanisms of the UPR is beyond the scope of this article, but several excellent reviews have been published (15,16). Briefly, the UPR occurs in response to endoplasmic reticulum (ER) stress, i.e., the presence of misfolded or unfolded proteins.…”

Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3-L1 adipocytes

“…This could be a target for understanding the etiology and complications of some causes of obesity [20]. Indeed, several hypotheses have been proposed as the cause for the initiation of inflammatory processes during obesity, including oxidative stress [14,23], endoplasmic reticulum stress [21,24,38], and adipose tissue hypoxia [48,59]. Therapies trying to manage and counterbalance some of these adipose tissue pro-inflammatory conditions are under investigation [16,39,50].…”

Genetics, physiology and perinatal influences in childhood obesity: view from the Chair

“…mitochondrial activity, increased oxidative and endoplasmic reticulum (ER) stress, 15 inflammatory cytokine levels, macrophage infiltrates 5,16 and increased necrotic death. 5 Elevated circulating FA levels are seen in obesity and are an independent cardiovascular risk factor.…”

“…59 ER stress is part of the metabolic syndrome. 15 In functional proteomic studies, an ER lipase, TGH, contributed the most non-HSL hydrolase activity in adipocyte cytoplasmic and fat cake fractions. 60 Knockdown of TGH in NIH-3T3 cells reduces basal lipolysis.…”